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Uracil is an unavoidable aberrant base in DNA sequences, the repair of which takes place by a highly efficient base excision repair mechanism. The removal of uracil from the genome requires multiple biochemical steps with conformational changes of DNA that inhibit DNA replication and interfere with transcription. However, the relevance of uracil in DNA for cellular physiology and transcriptional regulation is not fully understood. We investigated the functional roles of SMUG1 using knock-down (KD) and knock-out (KO) models. The proliferation ratio of SMUG1 KD and KO cells was decreased compared to WT control cells, and the cell cycle was arrested in the G2/M phases before the transition to mitosis. The apoptotic cell death was increased in KD and KO cell lines through the increase of BAX and active caspase 3 expression. Phospho-gamma-H2AX expression, which reflected accumulated DNA damage, was also increased in KO cells. Moreover, the apoptotic cells by DNA damage accumulation were markedly increased in SMUG1 KD and KO cells after ultraviolet C irradiation. Transcriptomic analysis using RNA-seq revealed that SMUG1 was involved in gene sets expression including cell cycle transition and chromatin silencing. Together, the results implicate SMUG1 as a critical factor in cell cycle and transcriptional regulation.Vision processing on traditional architectures is inefficient due to energy-expensive off-chip data movement. Many researchers advocate pushing processing close to the sensor to substantially reduce data movement. However, continuous near-sensor processing raises sensor temperature, impairing imaging/vision fidelity. We characterize the thermal implications of using 3D stacked image sensors with near-sensor vision processing units. Our characterization reveals that near-sensor processing reduces system power but degrades image quality. For reasonable image fidelity, the sensor temperature needs to stay below a threshold, situationally determined by application needs. Fortunately, our characterization also identifies opportunities-unique to the needs of near-sensor processing-to regulate temperature based on dynamic visual task requirements and rapidly increase capture quality on demand. Based on our characterization, we propose and investigate two thermal management strategies-stop-capture-go and seasonal migration-for imaging-aware thermal management. For our evaluated tasks, our policies save up to 53% of system power with negligible performance impact and sustained image fidelity.Despite the widespread availability of automated external defibrillators, not everyone is enthusiastic about using them. The aim of this study was to examine the reasons for not using an automated external defibrillator (AED) and predictors of the reasons. The study had a cross-sectional design using an online survey. Data were collected in eighteen districts in Hong Kong to be representative of the city. The questionnaire consisted of questions on demographics, knowledge and attitude towards AED use, reasons for not using AED, and whether the kind of victim could affect the decision of the bystanders. There was a high significant correlation between knowledge and attitude, with r = 0.782 and p less then 0.001. Of the respondents, 53.3% agreed that the kind of victim would affect their willingness to operate an AED. check details A binary logistic regression model revealed that a higher education (OR 6.242, 95% CI 1.827-21.331), concern about the kind of victim involved (OR 2.822, 95% CI 1.316-6.052), and a younger age were significant predictors of worrying about taking on responsibility in using AED. Other than knowledge, other barriers included a desire to avoid legal liability, and the kind of victim they encountered. Life experiences in adulthood could possibly affect the social responsibility and influence the behaviors of adults to operate AEDs.Chemokines are an extended group of chemoattractant cytokines responsible for the recruitment of leukocytes into tissues. Among them, interferon-γ-inducible protein 10 (CXCL10) is abundantly expressed following inflammatory stimuli and participates in the trafficking of monocytes and activated T cells into sites of injury. Here, we report that different members of the galectin family of carbohydrate-binding proteins promote the expression and synthesis of CXCL10 independently of interferon-γ. Interestingly, CXCL10 induction was observed when galectins came in contact with stromal fibroblasts isolated from human cornea but not other cell types such as epithelial, monocytic or endothelial cells. Induction of CXCL10 by the tandem repeat galectin-8 was primarily associated with the chemotactic migration of THP-1 monocytic cells, whereas the prototype galectin-1 promoted the CXCL10-dependent migration of Jurkat T cells. These results highlight the potential importance of the galectin signature in dictating the recruitment of specific leukocyte populations into precise tissue locations.Over the past decade, the one strain many compounds (OSMAC) approach has been established for the activation of biosynthetic gene clusters (BGCs), which mainly encode the enzymes of secondary metabolite (SM) biosynthesis pathways. These BGCs were successfully activated by altering various culture conditions, such as aeration rate, temperature, and nutrient composition. Here, we determined the biosynthetic potential of 43 bacteria using the genome mining tool antiSMASH. Based on the number of BGCs, biological safety, availability of deposited cultures, and literature coverage, we selected five promising candidates Bacillus amyloliquefaciens DSM7, Corallococcus coralloides DSM2259, Pyxidicoccus fallax HKI727, Rhodococcus jostii DSM44719, and Streptomyces griseochromogenes DSM40499. The bacteria were cultivated under a broad range of OSMAC conditions (nutrient-rich media, minimal media, nutrient-limited media, addition of organic solvents, addition of biotic additives, and type of culture vessel) to fully assess the biosynthetic potential. In particular, we investigated so far scarcely applied OSMAC conditions to enhance the diversity of SMs. We detected the four predicted compounds bacillibactin, desferrioxamine B, myxochelin A, and surfactin. In total, 590 novel mass features were detected in a broad range of investigated OSMAC conditions, which outnumber the predicted gene clusters for all investigated bacteria by far. Interestingly, we detected mass features of the bioactive compounds cyclo-(Tyr-Pro) and nocardamin in extracts of DSM7 and DSM2259. Both compounds were so far not reported for these strains, indicating that our broad OSMAC screening approach was successful. Remarkably, the infrequently applied OSMAC conditions in defined medium with and without nutrient limitation were demonstrated to be very effective for BGC activation and for SM discovery.
Read More: https://www.selleckchem.com/Proteasome.html
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